UNIVERSITY OF PENNSYLVANIA ALZHEIMER?S DISEASE CORE CENTER ABSTRACT: REVISION TO CREATE A NEW NEUROIMAGING CORE (CORE I) ADCC Director and Principal Investigator: John Q. Trojanowski, MD, PhD; Neuroimaging Core Leaders: John A Detre, MD and Paul A. Yushkevich, PhD This is an application for a revision of the University of Pennsylvania (Penn) Alzheimer Disease Core Center (ADCC) to establish an independent Neuroimaging Core (Core I). Currently, no dedicated neuroimaging infrastructure exists in Penn?s ADCC. Neuroimaging has emerged as a key approach for detecting and quantifying molecular neuropathology and resultant neurodegeneration in vivo, and neuroimaging biomarkers are contributing an increasing role to the diagnosis and prognosis of Alzheimer?s disease (AD) by staging patients along the AD continuum (i.e. preclinical through dementia). Advances in structural, functional, and molecular neuroimaging methodologies continue to expand the sensitivity, specificity, and appeal of these approaches, due in part to the non-invasiveness of image acquisition as compared to other potential biomarkers. The proposed Neuroimaging Core will create new infrastructure within the Penn ADCC to support state-of-the-art neuroimaging acquisition and informatics and provide ADCC investigators with access to resources and expertise needed to fully integrate neuroimaging metrics into clinical evaluation, clinical-pathological correlations, and genomic analyses. Aim 1 of the proposed Neuroimaging Core I will leverage leading neuroimaging expertise to support the development, acquisition, and analysis of state-of-the-art structural, functional, and molecular neuroimaging, including use of ultra-high-field imaging (7 Tesla) and novel PET ligands, and their applications as noninvasive biomarkers of AD neuropathology in the ADCC Clinical Core B cohort. As there is limited work linking quantitative measures of various proteinopathies and their interactions with three-dimensional structural brain changes across the cortical mantle, Aim 2 establishes linkage between in vivo neuroimaging and quantitative postmortem digital pathology via high-resolution MRI of intact autopsy brain specimens and image guided tissue sampling for digital pathology, in collaboration with Neuropathology Core D. Aim 3 will establish a new data infrastructure that will link multiscale in vivo, ex vivo, and digital microscopy imaging data with the extensive clinical, behavioral, and biofluid database maintained by Bioinformatics and Biostatistics Core C and enable flexible inquiry and discovery across clinical, pathological, genetic, and imaging modalities as well as facilitate data sharing. Training in Neuroimaging will also occur in collaboration with Education Core F.